BDH1

BDH1 Full Name

3-hydroxybutyrate dehydrogenase, type 1

BDH1 Introduction

BDH1 (3-hydroxybutyrate dehydrogenase type 1) is a mitochondrial enzyme that plays a central role in ketone body metabolism. The gene encoding BDH1 is located on human chromosome 3q29 and produces a protein of approximately 343 amino acids with a molecular weight of about 38 kDa. BDH1 is expressed in various human tissues, with the highest levels found in the liver, kidney, heart, and brain. The enzyme catalyzes the reversible interconversion of acetoacetate and (R)-3-hydroxybutyrate (beta-hydroxybutyrate) using NAD(H) as a cofactor. This reaction is the final step in ketone body synthesis in the liver and the first step in ketone body utilization in extrahepatic tissues. BDH1 is essential for maintaining the balance between the two major ketone bodies, acetoacetate and beta-hydroxybutyrate, which serve as alternative energy sources for the brain and peripheral tissues during periods of fasting, starvation, prolonged exercise, or adherence to a ketogenic diet. The enzyme is also involved in the metabolism of other hydroxybutyrate isomers and has been implicated in various physiological and pathological processes, including cancer, diabetes, and neurological disorders.

Figure 1. Strcuture of BDH1.

Role in Diabetes and Metabolic Syndrome
BDH1 plays a significant role in the pathophysiology of diabetes and metabolic syndrome. In insulin-deficient states such as type 1 diabetes and advanced type 2 diabetes, uncontrolled lipolysis leads to excessive fatty acid delivery to the liver, driving ketogenesis and potentially leading to diabetic ketoacidosis (DKA). BDH1 activity influences the ratio of beta-hydroxybutyrate to acetoacetate, which affects the severity of acidosis, as beta-hydroxybutyrate is a stronger acid than acetoacetate. Elevated beta-hydroxybutyrate levels are a hallmark of DKA and are used clinically to monitor disease severity and response to treatment.

BDH1 in Cancer Metabolism
Altered metabolism is a hallmark of cancer, and many tumor cells exhibit dysregulated ketone body metabolism. BDH1 has been implicated in several types of cancer, including glioblastoma, breast cancer, colorectal cancer, and hepatocellular carcinoma. In glioblastoma (GBM), the most aggressive primary brain tumor, BDH1 expression is often upregulated, and the enzyme promotes tumor growth by facilitating the utilization of ketone bodies as an alternative energy source, particularly under glucose-limited conditions. Inhibition of BDH1 in GBM cells reduces proliferation, induces apoptosis, and impairs tumor growth in mouse xenograft models. In breast cancer, high BDH1 expression correlates with poor prognosis and may contribute to metabolic adaptation in the tumor microenvironment. Conversely, in some cancer types, BDH1 expression is downregulated, suggesting context-dependent roles.

Alternate Names for BDH1

BDH1; 3-hydroxybutyrate dehydrogenase, type 1; 3 hydroxybutyrate dehydrogenase (heart, mitochondrial) , BDH; D-beta-hydroxybutyrate dehydrogenase, mitochondrial; SDR9C1; short chain dehydrogenase/reductase family 9C; member 1; 3 hydroxybutyrate dehydrogenase (heart, mitochondrial); BDH; D beta hydroxybutyrate dehydrogenase, mitochondrial